KR20220092914A - gene gun - Google Patents

Abstract

The accelerator module is coupled to the initiator module and generates supersonic waves from the subsonic waves generated by the initiator module. Ultrasonic waves deliver particles to cells within the tissue. The accelerator module may include a deflagration-detonation transition material and a detonation output material. An example of a deflagration-detonation transition material is copper(I)5-nitrotetrazolate. A separate example of a deflagration-detonation transition material is lead azide. An example of a detonation output material is pentaerythritol tetranitrate (PETN).

Description

gene gun

The present disclosure relates to devices and methods for gene therapy. More specifically, the present disclosure relates to an apparatus and method related to a biolistic particle delivery system for delivering exogenous DNA (transgene) to cells.

A gene gun accelerates small doped metal particles to the highest possible speed. Particles pass through tissue en route to target cells. Particles, having such a high speed and density, and being very small, penetrate the tissue without permanently damaging the tissue. Damage caused by particles is easily repaired by the tissue because the size of the penetration path is small. Upon reaching the target cell, doping (including DNA) is inserted into the cell's nucleus.

Further, Patent Document 1 discloses a gene gun that delivers a biological material into cells by accelerating a solution containing a biological material using a gas without using metal particles.

Japanese Patent Laid-Open No. 2004-236657

Currently, the practical limit for accelerating particles is the speed of sound in the gas medium used. The existing fastest technology is to accelerate particles in an atmosphere of helium to increase the speed of sound, thereby increasing the practical limit of particle velocity. This limits the effectiveness of existing gene guns by limiting the penetration (penetration) depth of the particle (the particle penetration (penetration) depth is a function of the particle velocity). The only other gas with a high speed of sound is hydrogen, but this leads to concerns about flammability.

In certain specific medical applications, it may be advantageous to use a biolistic particle delivery system. In certain embodiments, the gene gun relies on a detonation (explosion) phenomenon to achieve doped metal particle velocities that are faster than the speed of sound in any gas (gas). In certain embodiments, the gene gun generates a blast wave that passes through a wall or wall segment but does not destroy the wall. The blast wave passes through the wall at the speed of sound of the wall material. For example, in certain embodiments, the wall is stainless steel. For stainless steel, the speed of sound is 5,790 m/s. On the opposite side of the wall are doped metal particles. The doped metal particles are emitted at the initial velocity of the detonation (explosion) wave, that is, 5,790 m/s in the above example. This greatly exceeds the speed of sound in helium of 1,007 m/s.

One aspect is an accelerator module coupled to an initiator module and configured to generate supersonic waves from subsonic waves generated by the initiator module. Ultrasonic waves are configured to deliver particles to cells within a tissue. The accelerator module has a body that defines (defines, defines) a receptacle having a propagation axis and a bottom surface. The container includes a first portion and a second portion disposed between the first portion and the bottom surface. The accelerator module also includes a first material disposed in the first portion, a second material disposed in the second portion, and a wall segment defined at least in part between a bottom surface of the container and an exterior surface of the body; and a plurality of doped metal particles in contact and generally aligned with the bottom surface along the propagation axis. The first material and the second material are configured to be triggered by a subsonic wave generated by the initiator module to generate a supersonic wave. The supersonic wave is configured to pass through the wall segment and then accelerate the plurality of doped metal particles to a velocity.

In certain specific embodiments, the speed comprises supersonic speed.

In certain specific embodiments, the rate comprises a rate sufficient to penetrate (penetrate the cell) the cell in the tissue.

Certain particular aspects include wherein the first material is a deflagration-to-detonation material (DDT).

Certain specific embodiments include that the deflagration-detonation transition material comprises a dry explosive (dry explosive).

Certain particular embodiments include wherein the deflagration-detonation transition material comprises lead azide.

Certain specific embodiments include wherein the deflagration-detonation transition material comprises copper(I) 5-nitrotetrazolate (DBX-1).

Certain particular aspects include wherein the second material is a detonating output material.

A certain specific aspect includes that the said detonation output material is dry explosives (dry explosives).

Certain specific embodiments include wherein the detonation output material comprises pentaerythritol tetranitrate (PETN).

Certain particular aspects include wherein the wall segment comprises stainless steel.

Certain particular aspects include wherein the body includes wall segments.

Certain particular aspects include that the material of the wall segment is selected such that the wall segment does not rupture when a supersonic wave passes therethrough.

Certain particular aspects include that the thickness of the wall segment is selected such that the wall segment does not rupture when a supersonic wave passes therethrough.

Certain particular aspects include the body having a base and a cap. The cap is configured to secure to the base forming at least a portion of the container therebetween.

In certain particular aspects, the container further comprises being configured to receive at least a portion of the initiator module with the cap not secured to the base. The container is configured to secure the initiator module relative to the body when the cap is secured to the base.

Certain particular aspects include the body having an opening into the container. The opening has a size and shape such that a portion of the initiator module passes through the opening when the initiator module is connected to the accelerator module.

Certain particular aspects include wherein a portion of the initiator module is at least one electrical pin.

Certain specific aspects include wherein the body includes an injection canister (discharge tube) disposed on an opposite side of the wall segment as viewed from the container. The ejection barrel is aligned with the propagation axis (arranged in line). The plurality of doped metal particles are disposed in the injection barrel.

A specific aspect includes that the injection cylinder is a linear cylinder, and the cross section of the injection cylinder has the same size as that of the container.

Certain specific aspects include that the accelerator module is a component of a gene gun.

Certain particular aspects include wherein the first portion and the second portion are aligned (arranged in a line) along the propagation axis.

Certain specific aspects include that the bottom surface is perpendicular to the propagation axis.

Certain specific aspects further include an adhesive disposed on at least a portion of the outer surface of the body. The plurality of doped metal particles are suspended in the adhesive.

Certain specific aspects include a screen fixed to the main body at a position covering the plurality of doped metal particles, and the plurality of doped metal particles in the absence of supersonic waves to prevent the plurality of doped metal particles from passing through the screen. An adhesive disposed on the screen is further provided.

Certain specific aspects further include a seal. The container is also configured to receive at least a portion of the initiator module. The sealant is disposed within the container to form a seal with the initiator module.

Certain particular embodiments include the particles of the plurality of doped metal particles having a diameter of about 1 micrometer.

Certain specific aspects include the plurality of doped metal particles comprising gold.

Certain specific aspects include the plurality of doped metal particles comprising tungsten.

Certain specific embodiments include the plurality of doped metal particles comprising a chemical substance.

Certain specific embodiments include that the chemical substance is DNA.

Certain specific aspects include wherein the initiator module is an electro explosive device (EED).

Certain particular embodiments include wherein the electric detonator (EED) has an electric input and a chemical output.

Certain specific embodiments include that the chemical output is a mixture of zirconium and potassium perchlorate.

Certain particular aspects include wherein the electric detonator (EED) comprises a casing, and wherein the article output is disposed within the casing.

Certain specific aspects include that the casing is metal.

One aspect is an accelerator module defining (defining) a vessel having a body having a propagation axis and a bottom surface. The propagation axis passes through the bottom surface. The accelerator module also includes a material configured to at least partially generate a supersonic propagating detonation (detonation) wave upon being disposed within the vessel, and a wall segment defined at least in part between the bottom surface of the vessel and the exterior surface of the body. a wall segment sized to allow the detonation (explosive) wave to propagate therethrough without rupturing the wall segment, and disposed on the opposite side of the wall segment as viewed from the vessel and approximately parallel to the axis of propagation It has a plurality of doped metal particles that are aligned (arranged in a row).

One aspect is a method for delivering a plurality of doped metal particles to cells in a tissue using a portable device. The method comprises igniting a chemical charge (gunpowder) disposed within a portable device to generate a subsonic wave, propagating the subsonic wave along an axis toward a material disposed in the portable device, and discharging the material by the subsonic wave ignite to generate a supersonic wave, thereby continuously propagating the supersonic wave along the axis towards a wall segment of the portable device, and propagating the supersonic wave through the wall segment without rupturing the wall segment; impinging the supersonic wave on the plurality of doped metal particles after passing through the segment to accelerate the plurality of doped metal particles to a velocity.

Another aspect is a gene gun having a propagation axis extending between at least a chemical charge (gunpowder) and a plurality of doped metal particles. The gene gun includes a deflagration-to-detonation material (DDT) disposed approximately along the propagation axis, and a deflagration-to-detonation transition material disposed on an opposite side of the deflagration-detonation transition material as viewed from the chemical charge, the propagation axis being approximately thus comprising a disposed detonating output material and a wall segment separating the detonating output material from a plurality of the plurality of doped metal particles.

According to the technology according to the present disclosure, in an apparatus and method for delivering a plurality of doped metal particles to a cell, it is possible to provide a technology capable of increasing the speed of the metal particles delivered to the cell than in the prior art.

1 is a perspective view of an embodiment of a gene gun including a handle and an accelerator module or cartridge according to a preferred embodiment of the present invention. The accelerator module is installed on the handle and can be replaced after use.
Fig. 2 is a perspective view of the distal end of the accelerator module shown in Fig. 1, and shows an ejection canister containing a plurality of particles.
Fig. 3 is a perspective view of a proximal end of the accelerator module shown in Fig. 1 , showing at least one pin of the initiator for electrically coupling the accelerator module to the handle;
Fig. 4 is a side view of the accelerator module shown in Fig. 2, showing the cap and base of the accelerator module integrally fixed to form a container; The vessel houses at least a portion of the initiator and defines (defines) a chamber.
Fig. 5 is a plan view of the distal end of the accelerator module shown in Fig. 2, and shows a plurality of particles arranged in the injection cylinder.
Fig. 6 is a plan view of a proximal end of the accelerator module shown in Fig. 2, showing at least one pin configured to be connected to a connector of a handle;
FIG. 7 is an exploded perspective view of the accelerator module shown in FIG. 2 , and shows, for example, the initiator separated from the container.
FIG. 8 is a cross-sectional view through the accelerator module shown in FIG. 4 taken along section 8-8 of FIG. 4 , with both the initiator and chamber shown aligned with the injection barrel along the axis. A wall segment separates the chamber from the injection canister.
FIG. 9 is a cross-sectional view similar to FIG. 8 , except that at least one pin is connected to the connector of the handle and the distal end of the accelerator module is disposed against the tissue.
FIG. 10A is a fragmentary cross-sectional view similar to FIG. 9 , except that the accelerator module is ignited, with a supersonic shock wave passing through a wall segment and accelerating a plurality of particles out of the ejection canister and through tissue.
FIG. 10B is a fragmentary cross-sectional view similar to FIG. 9 , except that the accelerator module is ignited, with a supersonic shock wave passing through a wall segment and accelerating a plurality of particles out of the ejection canister and through tissue.
FIG. 10C is a fragmentary cross-sectional view similar to FIG. 9 , except showing the step in which the accelerator module is ignited, where a supersonic shock wave passes through a wall segment and accelerates a plurality of particles out of the ejection canister and through the tissue.
Fig. 11 shows another embodiment of an injection barrel including an adhesive for suppressing a plurality of particles from falling from the injection barrel before ignition of the accelerator module.
Fig. 12 is a view similar to Fig. 11, except that the screen is disposed across the distal end of the injection canister.
13 is a diagram for explaining propagation of energy via an accelerator module.

EMBODIMENT OF THE INVENTION Below, embodiment which concerns on this indication is described with reference to drawings. In addition, each structure in each embodiment, combinations thereof, etc. are an example, and addition, abbreviation, substitution, and other changes of a structure are possible within the range which does not deviate from the main point of this invention as appropriate. The present disclosure is not limited by the embodiment, but is limited only by the claims.

As a particle delivery object to which the doped metal particle is delivered (introduced) in this indication, a tissue is mentioned, for example, Preferably, it is a cell in the said tissue. Further, when the particle delivery target is a cell in a tissue, the particle delivery target may be a nucleus in the cell or an organelle (organel) in the cell.

Examples of the tissue include animal tissue and plant tissue. Examples of the animal include vertebrates, and specific examples include mammals (mammals), birds, reptiles, amphibians, and fish. Examples of the plants include seed plants and spore plants, examples of seed plants include angiosperms and oysters, and examples of spore plants include ferns, moss plants, and algae. When the tissue as the particle delivery target is an animal tissue, in addition to epithelial tissue, connective tissue, muscle tissue, nervous tissue, etc., for example, organs, organs, epidermis (stratum corneum, intradermal), dermis, subcutaneous tissue, muscle and the like. When the tissue as the particle delivery target is a plant tissue, meristem (eg, apical meristem, cambium, etc.), permanent tissue (eg, epidermal tissue, ductal tissue, mechanical tissue, parenchyma, etc.), etc. In addition to those listed, it may include, for example, roots, stems, leaves, and the like.

The particle delivery target may be any of an in vitro system, an in vivo system, and an ex vivo system. That is, the particle delivery target may be in a state existing within the individual (living body), or may be in a state in which it has been extracted or separated from the individual (living body). The latter is a state in which the particle delivery target does not exist in an individual (living body), and as a specific example, when the particle delivery target is a cell (preferably, a cell in a tissue), the cell (preferably, Cells in a tissue) may be an aspect in which cells in a state existing in an individual (living body) (preferably cells in a tissue) are excluded. The individual (living body) may be either an animal individual (living organism) or a plant individual (living organism), and the aspects of animals and plants are as previously described. When the said individual (living body) is an animal individual (living body), Preferably it is a vertebrate individual (living body), More preferably, it is a mammalian individual (living body). Although it does not restrict|limit especially as a mammal, Humans, mammals except humans, etc. are mentioned. Examples of the human include a normal person and a person (patient) afflicted with a disease or the like. Examples of mammals other than humans include mice, rats, guinea pigs, hamsters, cattle, goats, sheep, pigs, monkeys, dogs, and cats.

In addition, the accelerator module according to the present disclosure includes a container having a propagation axis, a material disposed in the container and ignited by the subsonic wave generated by the initiator module to generate a supersonic wave, and the inside and outside of the container through the propagation axis. a wall segment, the outer surface of the wall segment being disposed to align a plurality of doped metal particles along a propagation axis, the material generating the supersonic wave having a plurality of doped particles after the supersonic wave generated by the material propagates and passes through the wall segment; It has a configuration in which the plurality of doped metal particles are accelerated by colliding with the metal particles. The initiator module has, for example, a chemical charge (gunpowder), and generates a deflagration that is a subsonic wave by igniting and burning the chemical charge by receiving the supply of operating power and operating it. The deflagration, which is a subsonic wave generated by the initiator module, propagates along the propagation axis toward the supersonic wave generating material accommodated in the container, and is ignited by deflagration where the material is a subsonic wave. When a material that generates a supersonic wave is ignited, a detonation (explosion) wave, which is a supersonic wave, is generated, and the detonation wave, which is a supersonic wave, travels along a propagation axis to a wall segment. A detonation wave (supersonic wave) that has reached the wall segment propagates (passes through) the interior of the solid wall segment, arrives at the outer surface of the wall segment, and collides with a plurality of doped metal particles disposed on the outer surface. As a result, the metal particles impart acceleration energy from the detonation wave (supersonic wave), and the metal particles are ejected at high speed and delivered to the target object for delivery of the particles.

The chemical charge of the initiator module may be, for example, zirconium or potassium perchlorate, or a mixture thereof. Of course, the chemical charge is not limited thereto, and various explosives capable of generating a deflagration that is a subsonic wave by ignition and combustion can be used. For example, the chemical charge according to the present disclosure is suitably applicable to the chemical charge used in an initiator used to inflate an airbag for a vehicle.

Moreover, although it does not specifically limit also about the material which produces|generates a supersonic wave by being ignited by a subsonic wave, Various dry explosives can be employ|adopted suitably. A material that generates a supersonic wave by being ignited by a subsonic wave can be grasped as a material for transitioning deflagration to detonation. Materials that generate supersonic waves by being ignited by subsonic waves suitably include, for example, lead azide, copper(I)5-nitrotetrazolate (DBX-1), pentaerythritol tetranitrate (PETN), and the like. of course, it is not limited to these, and various explosives can be employ|adopted. In addition, the container of the accelerator module may contain a plurality of types of materials for generating the supersonic waves. For example, the material which generates a supersonic wave by being ignited by a subsonic wave contains a 1st material and a 2nd material, and may be arrange|positioned so that these may align along a propagation axis in a container. A different type of explosive material may be sufficient as a 1st material and a 2nd material, and the same type of explosive material may be sufficient as it.

The wall segments of the accelerator module solidly propagate the detonation wave as a supersonic wave generated within the vessel. Here, the speed of sound is the speed of sound transmitted through a substance (medium), and it varies depending on the medium, and the speed of sound can be significantly increased in the case of using a solid as the medium compared to the case of using a gas as the medium. For example, the speed of sound in stainless steel reaches several times the speed of sound in helium gas. Of course, the material used for the wall segment is not limited to stainless steel. The wall segment may be formed of, for example, aluminum or another metal, or may be formed of a material other than the metal. The wall segments thus formed can further accelerate the detonation wave, for example, as a supersonic wave that has entered along the propagation axis, by means of solid propagation. And by making a supersonic wave (detonation wave) which reached the outer surface of a wall segment collide with a metal particle, for example, a metal particle can be inject|emitted at supersonic speed. In this way, the accelerator module and the gene gun provided with the accelerator module according to the present disclosure provide an accelerator module or a gene gun that is more practical by increasing the injection speed of metal particles than before.

1 is a perspective view of an embodiment of a gene gun 10 including a handle 11 and an accelerator module or cartridge 12 according to a preferred embodiment of the present invention. The accelerator module 12 is attached to the handle 11 and can be replaced after use. The specific embodiment in the gene gun 10 can be used in a research institute or a medical facility for transplanting DNA into a cell nucleus. The cell nucleus may be of a plant or an animal. For example, the cell nucleus may be that of a patient (human).

In certain specific embodiments, the accelerator module 12 includes a body 14 and an initiator 30 . In certain particular embodiments, the initiator 30 is attached to the body 14 . For example, in certain particular embodiments, body 14 defines (prescribes) a container (shown most clearly in FIG. 8 ) sized and shaped to receive at least a portion of initiator 30 . In certain specific embodiments, the body 14 and the initiator 30 are separately assembled to the frame. The frame is configured to fix the position of the body 14 relative to the position of the initiator 30 .

In certain particular embodiments, at least a portion of body 14 comprises a material selected based at least in part on material strength. In certain specific embodiments, the material is selected such that the body 14 is capable of encapsulating forces caused by an explosion occurring within the body 14 . In this way, the material exhibits sufficient strength to enclose the explosive force within the body 14 . In certain particular embodiments, at least a portion of body 14 comprises metal. Of course, the body 14 need not include metal, but may instead include a non-metal material or a combination of non-metal materials. For example, in certain particular embodiments, body 14 includes a plurality of materials.

2 is a perspective view of the distal end of the body 14 of the accelerator module 12 of FIG. In certain specific embodiments, the plurality of particles 60 are doped metal particles. In certain specific embodiments, the plurality of particles 60 move freely in the tissue without interfering with them.

In certain particular embodiments, body 14 includes wall segments 44 (shown most clearly in FIG. 8 ). In certain particular embodiments, the wall segment 44 is part of the body 14 and separates the container 20 from the plurality of particles 60 . In certain particular embodiments, the gene gun 10 generates a detonation wave (blast wave) that travels through the wall segment 44 of the accelerator module 12 , but prevents the wall segment 44 from rupturing.

In certain particular embodiments, the wall segment 44 does not rupture when the blast wave passes therethrough, thus maintaining a barrier between the detonating (explosive) material and the tissue. In certain particular embodiments, the wall segments 44 of the body 14 rupture when the plurality of particles 60 are ejected (emitted) from the ejection canister 58 , for example because of the size and shape of the rupture. , sufficiently attenuates the loss of pressure from the gene gun 10 . As a result, the plurality of particles 60 still have an initial velocity greater than the speed of sound before entering the tissue.

The detonation wave (blast wave) travels through the wall segment 44 at the speed of sound in the wall material before exiting (exiting from the wall segment 44 ). The outgoing detonation wave (blast wave) collides with the plurality of particles 60 , and an initial velocity approximately equal to the speed of the detonation wave (blast wave) when the detonation wave (blast wave) passes through the wall segment 44 to accelerate the plurality of particles 60 . As the detonation wave (blast wave) passes through the wall segment 44, as opposed to passing through the gas (gas), the speed of the detonation wave (blast wave) increases to a value greater than the speed of sound as it passes through the gas .

In a specific embodiment, at least a part of the main body 14 in the accelerator module 12 includes a material having a large sound velocity (a material having a large sound velocity). In certain specific embodiments, the greater (faster, higher) the speed of sound when passing through the material, the greater the initial velocity of the plurality of particles 60 ejected from the ejection canister 58 .

In certain specific embodiments, wall segment 44 has a thickness of 1 mm. In certain specific embodiments, wall segment 44 has a thickness of 0.5 mm. In certain specific embodiments, wall segment 44 has a thickness of 2 mm. In certain particular embodiments, the wall segments 44 have varying or non-uniform wall thicknesses. This disclosure is not limited to the recited values, but includes any other value for thickness. In certain particular embodiments, the material of the wall segment 44 is selected based at least in part on the speed of sound through the wall segment 44 . In certain particular embodiments, the material of the wall segment 44 is such that the body 14 accelerates the plurality of particles 60 to an initial velocity sufficient to penetrate (penetrate) the tissue to a desired depth. chosen to be In this way, the material of the wall segment 44 exhibits a sufficient speed of sound for the plurality of particles 60 to reach the desired depth in the tissue. In certain specific embodiments, the first portion of the body 14 includes a material having sufficient strength to enclose the explosive force. On the other hand, similarly, the second part of the main body 14 has a speed of sound sufficient to accelerate the plurality of particles 60 to a speed of sound sufficient for the plurality of particles 60 to reach a desired depth in the tissue. includes materials.

FIG. 3 is the accelerator module 12 shown in FIG. 1 showing at least one pin 38 (electrical input) of the initiator 30 for electrically coupling the accelerator module 12 to the handle 11 . is a perspective view of the proximal end of In certain particular embodiments, accelerator module 12 is embedded in gene gun 10 by any means desired. As discussed below, in certain specific embodiments, firing pulses are provided at desired times using an electrical firing mechanism, such as initiator 30 .

FIG. 4 is a side view of the accelerator module 12 shown in FIG. 2 . In the illustrated embodiment, the body 14 of the accelerator module 12 has a base 16 and a cap 18 . In another embodiment, the body 14 is fabricated as a single monolithic structure. In another embodiment, the body 14 of the accelerator module 12 is assembled from three or more structures.

In certain specific embodiments, base 16 and cap 18 have complementary engaging structures 22 . The engaging structure 22 is configured to integrally fix the base 16 and the cap 18 . In certain particular embodiments, the engaging structure 22 includes one or a plurality of welds, adhesives, fasteners, mechanical locks, screws, or any other structure capable of securing the base 16 to the cap 18 . do. In another embodiment, rather than directly securing the base 16 and the cap 18 , a frame is used to secure the base 16 relative to the cap 18 .

5 is a top plan view of the distal end of the accelerator module 12 shown in FIG. 2 , and a plurality of particles 60 disposed against an outer surface 56 (shown most clearly in FIG. 8 ) of the body 14 . ) is shown. In certain specific embodiments, the outer surface 56 is a part of the concave shape in the body 14 . In certain specific embodiments, the concave shape has the form of an ejection tube (discharge tube) 58 . In certain specific embodiments, a plurality of particles ( 60 ) are supported by at least an outer surface ( 56 ) of an ejection canister ( 58 ). In certain specific embodiments, at least a portion of the bore forming the tubular (tubular) wall of the injection barrel 58 supports the plurality of particles 60 .

In certain specific embodiments, the outer surface 56 is not part of the concave shape, but instead part of the convex shape in which the plurality of particles 60 are disposed. In certain specific embodiments, the outer surface 56 on which the plurality of particles 60 are disposed has a planar shape.

In certain specific embodiments, the plurality of particles 60 are attached to at least the outer surface 56 . In certain specific embodiments, a plurality of particles 60 are disposed on the outer surface 56 . In certain specific embodiments, a plurality of particles 60 are deposited (stacked) on the outer surface 56 . In certain specific embodiments, a plurality of particles 60 are randomly disposed on the outer surface 56 .

In certain specific embodiments, the plurality of particles 60 are metal particles. In certain specific embodiments, the plurality of particles 60 include small metal particles. In a specific embodiment, each particle in the plurality of particles 60 has a size on the order of 1 micrometer. In a specific embodiment, each particle in the plurality of particles 60 has a size on the order of 2 micrometers. Of course, the size of the particle|grains in the some particle|grain 60 is not limited to this, Another size may be sufficient.

In certain particular embodiments, the particles of the plurality of particles 60 have a spherical shape. In another embodiment, the particles of the plurality of particles 60 have a conical shape. In another embodiment, the particles of the plurality of particles 60 have a cylindrical shape. In another embodiment, the particles of the plurality of particles 60 have a cubic shape. In another embodiment, the particles of the plurality of particles 60 have a mixture of two or more shapes.

In certain particular embodiments, the particles of the plurality of particles 60 are homogeneous. In a specific embodiment, at least some particles among the plurality of particles 60 are different in size and shape from other particles.

In certain specific embodiments, the plurality of particles 60 is made of a high-density material. For example, in certain specific embodiments, the high-density material is gold, tungsten, or other known high-density material. In certain specific embodiments, it may be desirable for the plurality of particles 60 to contain a high density that, when accelerated at the same speed, increases the kinetic energy of the plurality of particles 60 rather than a particle with a lower density. .

In certain specific embodiments, a plurality of particles 60 are doped. In certain specific embodiments, a chemical is attached to the particle. In certain specific embodiments, the plurality of particles 60 is coated with a chemical substance. In certain specific embodiments, the chemical agent comprises DNA. In certain specific embodiments, the DNA is plasmid DNA. In certain specific embodiments, the DNA is a circular double-stranded DNA molecule. In certain specific embodiments, the plurality of doped particles 60 are particles coated with DNA and having a size smaller than that of a cell. In certain specific embodiments, the DNA is chromosomal DNA.

In certain specific embodiments, the ejection barrel 58 can output the plurality of particles 60 in a predetermined direction. For example, the ejection canister 58 may output a plurality of particles 60 along the axis 28 . In certain particular embodiments, axis 28 is a propagation axis. In some embodiments, the ejection barrel 58 can direct the plurality of particles 60 to a predetermined location on the tissue.

In certain specific embodiments, the ejection canister 58 has a constant inner diameter. In certain specific embodiments, the ejection barrel 58 has an inner diameter that converges in the ejection direction (the ejection direction). In certain specific embodiments, the ejection canister 58 has an inner diameter that diverges in the ejection direction. In a specific embodiment, the injection cylinder 58 has an inner diameter that converges in the injection direction and then diverges in the injection direction.

In certain specific embodiments, the ejection canister 58 may have one or more deflection plates (blades, vanes) formed in the inner wall of the bore of the ejection canister 58 . In a specific embodiment, one or a plurality of deflection plates are sized and shaped to straighten a plurality of particles 60 ejected from the gene gun 10 . The vane can reduce turbulence in the plurality of particles 60 when the plurality of particles 60 are ejected from the injection barrel 58 .

In certain specific embodiments, the gene gun 10 injects a plurality of doped particles 60 into tissues, cells, and/or organelles. In certain specific embodiments, injection of the plurality of doped particles 60 is performed in vitro (externally). In certain other specific embodiments, injection of the plurality of doped particles 60 is performed in vivo (in vivo). In a specific embodiment, the gene gun 10 injects a plurality of doped particles 60 into the cell nucleus.

When the plurality of particles 60 are injected, preferably the plurality of particles 60 penetrate into the tissue. In a specific embodiment, the plurality of particles 60 injected by the gene gun 10 penetrate the tissue to a desired depth in the tissue. In certain specific embodiments, the desired depth is predefined. In certain particular embodiments, the desired depth is determined based, at least in part, on the composition (configuration) of the plurality of particles 60 . For example, the desired depth may be different for different accelerator modules 12 .

FIG. 6 is a plan view of the proximal end of the accelerator module 12 shown in FIG. 2 , showing at least one pin 38 of the initiator 30 configured to connect to the connector 40 of the handle 11 . In certain specific embodiments, at least one fin 38 includes two conductive fins. In certain specific embodiments, the two conductive pins are gold plated. In certain specific embodiments, at least one pin 38 of the initiator 30 is electrically connected to the connector 40 .

In certain specific embodiments, the initiator 30 is ignited by an electrical input. In certain particular embodiments, at least one pin 38 receives an electrical input in the form of an electrical ignition pulse. In certain particular embodiments, the gene gun 10 includes one or more electronic components for operating the initiator 30 . In certain specific embodiments, the one or more electronic components are supported by a gene gun (10).

In certain particular embodiments, the one or more electronic components are configured to generate a current to actuate the initiator 30 . In certain specific embodiments, the one or more electronic components include a controller. In certain particular embodiments, the gene gun 10 has an interface for a user to activate the one or more electronic components to activate the initiator 30 . In certain specific embodiments, the interface is a pull trigger.

In certain specific embodiments, the gene gun 10 includes an energy source for one or more electronic components. In certain specific embodiments, the energy source is supported by the handle 11 . In certain specific embodiments, the energy source may be a battery. In certain specific embodiments, the battery supplies power to one or more electronic components to ignite the initiator 30 .

In certain specific embodiments, a battery or other electrical energy source provides an electrical ignition pulse to initiator 30 via connector 40 . In one particular embodiment, the magnitude and duration of the electrical ignition pulse applied to the initiator 30 is 1.2 amps and 2 ms. In one particular embodiment, the magnitude and duration of the electrical ignition pulse applied to initiator 30 is 1.75 amps and 0.5 ms. This disclosure is not limited to the recited values, but includes any other values relating to the above magnitude and duration. In certain particular embodiments, the magnitude and duration of the electrical ignition pulses applied to the initiator 30 are selected based, at least in part, on the operating characteristics of the initiator 30 .

FIG. 7 is an exploded perspective view of the accelerator module 12 shown in FIG. 2 , and shows, for example, the initiator 30 separated from the container 20 . In certain specific embodiments, the initiator 30 can be any electric detonator (EED). In certain specific embodiments, the initiator 30 includes a chemical charge 34 (a chemical output). The chemical charge 34 is configured to generate a flame when ignited. In certain specific embodiments, the initiator 30 includes a casing 32 . In certain specific embodiments, the casing 32 includes a chemical charge 34 . In certain specific embodiments, the initiator 30 is an initiator for an automobile. Examples of the initiator for automobiles include initiators used for airbags for automobiles.

In certain specific embodiments, container 20 is formed by base 16 and cap 18 . In certain particular embodiments, base 16 comprises at least a portion of container 20 . In certain particular embodiments, cap 18 comprises at least a portion of container 20 . In certain particular embodiments, at least a portion of the initiator 30 is disposed within the container 20 . In certain specific embodiments, base 16 and cap 18 are integrally secured to form a container. In certain particular embodiments, after the initiator 30 is placed in the container 20 , the base 16 and the cap 18 are integrally secured.

In certain particular embodiments, the container 20 is sized and shaped such that the initiator 30 prevents movement of the initiator 30 relative to the container 20 when the cap 18 is secured to the base 16 . Its size and shape are determined with respect to. In this way, the initiator 30 can be locked (fixed) in the container 20 at least when the base 16 and the cap 18 are integrally fixed.

FIG. 8 is a cross-sectional view through the accelerator module 12 shown in FIG. 4 taken along section 8-8 of FIG. 4 , with the initiator 30 aligned along the axis 28 (arranged in line). Both the chamber 45 and the injection cylinder 58 are shown. In certain specific embodiments, the chamber 45 is a part of the container 20 and is disposed between the initiator 30 and the bottom surface 54 of the container 20 . A wall segment 44 separates the chamber 45 from the injection canister 58 .

In certain particular embodiments, the connector 40 is structurally secured to the body 14 . In certain particular embodiments, body 14 has a lip 42 configured to capture a portion of connector 40 and structurally secure connector 40 to body 14 . In certain specific embodiments, the user can detach or remove the connector 40 from the main body 14 . For example, after the accelerator module 12 is used, the connector 40 can be removed from the main body 14 , the used accelerator module 12 can be removed, and it can be replaced with a new accelerator module 12 . have.

In certain specific embodiments, the container 20 has an opening 26 . In certain specific embodiments, an opening 26 is disposed in the base 16 . In certain specific embodiments, the opening 26 is disposed between the surface of the initiator 30 and the surface of the base 16 . In certain specific embodiments, at least a portion of the initiator 30 passes through an opening 26 in the base 16 before the cap 18 is secured to the base 16 to form the complete container 20 . .

In certain particular embodiments, initiator 30 includes resistive element 36 . In a specific embodiment, the resistance element 36 is disposed with respect to the casing 32 . In certain specific embodiments, an electrical ignition pulse applied to the initiator 30 heats the resistive element 36 in the initiator 30 . In one embodiment, the resistance element 36 is sufficiently heated by the electric ignition pulse to ignite the chemical charge (explosive) 34 in the casing 32 . In certain specific embodiments, the chemical charge 34 is a mixture of zirconium and potassium perchlorate. In certain specific embodiments, the chemical charge 34 is a single material or a mixture with other materials.

In certain specific embodiments, the casing 32 is made of metal. In certain specific embodiments, the metal is stainless steel. Of course, the casing 32 may be made of any other metal in addition to stainless steel. In certain specific embodiments, the metal is aluminum. In certain specific embodiments, the casing 32 is made of a polymer. In certain particular embodiments, the material and thickness of the casing 32 is selected such that the material ruptures in response to the pyrotechnic charge 34 being ignited. Rupture of the casing 32 allows the flame to escape from the casing 32 and travel or propagate at subsonic speed along the axis 28 towards the chamber 45 .

In certain particular embodiments, the flame exiting the casing 32 ignites the material within the chamber 45 . When the chemical charge 34 is ignited, the pressure released by the chemical charge 34 in the casing 32 destroys the casing 32 , the deflagration propagates at subsonic speed along the axis 28 and the chamber (45) Ignite the material within.

In certain specific embodiments, the accelerator module 12 includes a seal 24 . In certain specific embodiments, the sealant 24 is a gasket, an o-ring, or other suitable structure. In certain specific embodiments, the sealant 24 is disposed between one or more surfaces of the body 14 and one or more surfaces of the initiator 30 . In certain specific embodiments, sealant 24 is disposed within opening 26 . In certain specific embodiments, the sealing material 24 suppresses the flame escaping from the casing 32 from leaking toward the connector 40 through the opening 26 when the initiator 30 is ignited. In certain specific embodiments, when the sealant 24 is ignited by a flame escaping from the casing 32 through rupture, the material exploding in the chamber 45 passes through the opening 26 to the connector 40 . to prevent leakage toward

In certain particular embodiments, the material in the chamber 45 is selected to produce a detonating wave when the material is ignited by a flame caused by the ignition of the chemical charge 34 . . In certain specific embodiments, the detonation (explosion) wave travels at a speed greater than the speed of sound.

In certain specific embodiments, in order to achieve the desired detonation (explosion) wave from chamber 45, the rate of the overall pyrotechnic reaction, initially subsonic deflagration caused by ignition of pyrotechnic charge 34, is ) by the explosion of the material in it, it is increased to be greater than the speed of sound. In certain specific embodiments, one or more materials are disposed within chamber 45 to generate a desired detonation (burst) wave.

For example, in certain specific embodiments, the material comprises a deflagration to detonation transition (DDT) material and a detonating output material. In certain specific embodiments, each of the materials is disposed in at least a portion of the chamber 45 . In certain specific embodiments, the material is one or more of lead azide, copper(I)5-nitrotetrazolate (DBX-1), and pentaerythritol tetranitrate (PETN). Of course, the present disclosure is not limited to the enumerated materials or combinations of materials, and other materials or combinations of materials that produce the desired detonation (explosive) wave may be used.

In certain specific embodiments, the material includes at least a first material 48 and a second material 52 . The first material 48 and the second material 52 may be disposed in the first portion 46 and the second portion 50 of the chamber 45 , respectively. In certain specific embodiments, the first material 48 is separated from the second material 52 within the chamber 45 . In certain particular embodiments, the first material 48 contacts the second material 52 at the interface. In certain specific embodiments, the first material 48 is separated from the second material 52 by a barrier (barrier). In certain specific embodiments, the barrier is a temporary barrier between the first material 48 and the second material 52 . For example, when the first material 48 ignites, the barrier ruptures. In certain specific embodiments, the first material 48 is disposed around the perimeter of the second material 52 . In certain particular embodiments, the first material 48 and the second material 52 form a mixture within the chamber 45 .

In certain specific embodiments, the interface between the first material 48 and the second material 52 is disposed perpendicular to the axis 28 . In certain specific embodiments, the location of the interface promotes propagation of a detonation (explosive) wave towards the wall segment 44 along the axis 28 . In certain specific embodiments, the interface is not disposed perpendicular to the axis 28 . In certain particular embodiments, the size of the area of contact between the first material 48 and the second material 52 is selected to facilitate detonation of the second material 52 by the first material 48 . In certain specific embodiments, the interface may be smooth. In a specific embodiment, the interface may be bumpy.

In the illustrated embodiment, the first portion 46 is disposed closer to the initiator 30 than the second portion 50 . In the illustrated embodiment, the second portion 50 is disposed between the first portion 46 and the wall segment 44 .

In certain specific embodiments, the ratio of the first material 48 to the second material 52 is 50/50. Of course, other ratios are within the scope of the present disclosure. For example, in certain specific embodiments, the ratio of the first material 48 to the second material 52 is 40/60. For example, in certain specific embodiments, the ratio of the first material 48 to the second material 52 is 60/40.

In certain particular embodiments, the first material 48 is a deflagration-detonation transition (DDT) material. In certain specific embodiments, the first material 48 is a dry explosive. In certain specific embodiments, the first material 48 is a lead azide material. In certain specific embodiments, the first material 48 is a copper(I)5-nitrotetrazolate (DBX-1) material.

In certain specific embodiments, the second material 52 is a detonation output material. In certain specific embodiments, the second material 52 is a dry explosive. In certain specific embodiments, the second material 52 is pentaerythritol tetranitrate (PETN). In certain specific embodiments, the detonate wave generated by the PETN travels at a speed greater than the speed of sound. In certain specific embodiments, the detonation (detonation) wave generated by the PETN generates a similar detonation (detonation) wave within the wall segment 44 .

In certain specific embodiments, the detonation (explosive) wave continues through the wall segment 44 to impart its velocity to a plurality of particles 60 disposed with respect to the exterior surface 56 of the body 14 . . The detonation (explosion) wave then ejects (discharges) the plurality of particles 60 from the main body 14 at an initial velocity exceeding the speed of sound. In certain specific embodiments, the plurality of particles 60 are ejected with an initial velocity equal to the velocity of the detonation (explosive) wave passing through the wall segment 44 .

FIG. 9 is a cross-sectional view similar to that of FIG. 8 , except that at least one pin 38 is connected to the connector 40 of the handle 11 and the distal end of the accelerator module 12 is disposed with respect to the tissue. to be. 10A-10C illustrate the steps in which the accelerator module 12 is ignited, wherein a supersonic shock wave passes through the wall segment 44 and accelerates the plurality of particles 60 out of the injection canister 58 and through the tissue. Except that, it is a partial cross-sectional view similar to that of FIG. 9 .

Fig. 10A shows that the initiator 30 is being actuated (ignited) by an electrical input. In certain particular embodiments, at least one pin 38 receives an electrical input in the form of an electrical ignition pulse. The initiator 30 includes a chemical charge 34 . The chemical charge 34 generates a flame upon ignition. When the chemical charge 34 is ignited, the pressure released by the chemical charge 34 in the casing 32 destroys the casing 32, and deflagration causes the first material in the chamber 45 along the axis 28 ( 48) to make it possible to propagate at subsonic speed. The deflagration caused by the pyrotechnic charge 34 creates a propagating subsonic flame. In this way, the subsonic flame travels towards the chamber 45 .

FIG. 10B shows an exiting deflagration that ignites the first material 48 in the chamber 45 . In certain particular embodiments, the first material 48 is a deflagration-detonation transition (DDT) material. Upon ignition, the first material 48 transitions (transitions) from deflagration to detonation (detonation). As the first material 48 is ignited by the subsonic flame, the subsonic flame finally transitions to a detonation (explosion). In this way, the subsonic flame entering the first material 48 emerges from the first material 48 as a supersonic flame. The flame front surface accelerates and becomes a supersonic flame propagating towards the second material 52 . With the transition from flame (detonation) to detonation (explosion), the pressure increases. The detonation (explosion) causing the supersonic wave creates a strong pressure wave propagating in front of the propagating flame which causes the temperature of the first material to be higher than the self-ignition temperature of the first material 48 .

10C shows the detonation (explosion) of the second material 52 resulting from the detonation (explosion) of the first material 48 . In a specific embodiment, the detonation (explosion) wave generated by the second material 52 travels at a speed greater than the speed of sound. The detonation (detonation) wave generated by the second material 52 creates a similar detonation (detonation) wave in the wall segment 44 . The detonation (explosive) wave continues through the wall segment 44 , imparting its velocity to a plurality of particles 60 disposed against the outer surface 56 of the body 14 . The detonation (explosion) wave then ejects (discharges) the plurality of particles 60 from the main body 14 at an initial velocity exceeding the speed of sound.

Hereinafter, a method of manufacturing the accelerator module 12 will be described. Of course, other methods involving more or fewer steps, and/or different orders of steps, are also within the scope of the present disclosure.

In certain particular embodiments, a method for manufacturing an accelerator module 12 is disclosed by providing a base 16 . The base 16 has a chamber 45 formed in part by a bottom surface 54 . The bottom surface 54 is spaced apart from the exterior surface 56 by a wall segment 45 . The distal end of the ejection canister 58 is configured to be positioned against tissue. In certain specific embodiments, the ejection barrel 58 is configured to support the plurality of particles 60 .

A second material 52 is loaded into the second portion 50 of the chamber 45 . In certain specific embodiments, the second material 52 is in contact with the bottom surface 54 . In certain specific embodiments, the second material 52 is a detonation output material. In certain specific embodiments, the second material 52 is a dry explosive. In a particular embodiment, the second material 52 is pentaerythritol tetranitrate (PETN). In certain particular embodiments, the second material 52 is pressed against the bottom surface 54 of the chamber 45 at a pressure necessary to achieve the desired degree of compressibility.

The first material 48 is the first portion 46 of the chamber 45 and is loaded on top of the second material 52 . In certain specific embodiments, the first material 48 is in contact with the second material 52 . In certain specific embodiments, the first material 48 is a deflagration-detonation transition material. In certain specific embodiments, the first material 48 is a dry explosive. In certain specific embodiments, the first material 48 is lead azide. In certain specific embodiments, the first material 48 is copper(I)5-nitrotetrazolate (DBX-1). In certain particular embodiments, the first material 48 is urged against the second material 52 within the chamber 45 at a pressure necessary to achieve the desired degree of compressibility. Of course, the first material 48 and the second material 52 may be press-fitted into the chamber 45 at the same time to achieve the desired degree of compressibility without pressing separately.

Then, the initiator 30 is installed in the opening 26 of the base 16 . In certain specific embodiments, at least a portion of the casing 32 is disposed within the chamber 45 of the container 20 . In certain specific embodiments, the casing 32 is disposed proximate the first material 48 .

In certain specific embodiments, the initiator 30 is provided in the opening 26 of the base 16 together with the sealing material 24 . In certain specific embodiments, the sealant 24 is a gasket or O-ring. In a specific embodiment, the initiator 30 is held at a predetermined position by providing the cap 18 . In certain specific embodiments, cap 18 has threads complementary to threads in base 16 .

The plurality of particles 60 are installed in the injection cylinder 58 . When the gene gun 10 is used with the ejection barrel 58 facing upward, the plurality of particles 60 are injected onto the exposed main body 14, and the main body 14 is moved by gravity. may be held against the outer surface 56 . In certain specific embodiments, the plurality of particles ( 60 ) are injected on the outer surface ( 56 ) of the body ( 14 ) in the injection barrel ( 58 ).

In a specific embodiment, in order to use the gene gun 10 in an arbitrary direction, the plurality of particles 60 is held at a predetermined position with respect to the outer surface 56 of the main body 14 . In this way, the detonation (explosion) wave which radiates|emits the wall segment 45 will be transmitted to the some particle|grain 60. As shown in FIG.

11 shows another embodiment of an ejection canister 58 that includes an adhesive 62 for inhibiting a plurality of particles 60 from falling from the ejection canister 58 prior to ignition of the accelerator module 12 . . The adhesive 62 holds the plurality of particles 60 at a predetermined position with respect to the outer surface 56 . In certain specific embodiments, when the gene gun 10 is manipulated, the adhesive 62 can collapse and/or evaporate leaving behind a plurality of particles 60 that can continue to travel at the speed of the detonation (explosive) wave. have. In certain specific embodiments, the adhesive 62 has a lower density than the plurality of particles 60 and disperses or decelerates rapidly. In this way, the adhesive 62 does not interfere with the movement of the plurality of particles 60 .

FIG. 12 is similar to FIG. 11 except that a screen (cover) 64 is disposed across and secured to the distal end of the ejection canister 58 . In the illustrated embodiment, adhesive 62 is held on screen 64 . In certain specific embodiments, screen 64 has a plurality of pores. In a specific embodiment, the plurality of pores are micro pores. In certain specific embodiments, the screen 64 has fine gratings (slits) that allow the pores of the screen 64 to pass without interfering with the plurality of particles 60 .

13 is a diagram illustrating a method for propagating energy through the accelerator module 12 . This method uses a portable device such as the gene gun 10 to deliver (introduce) a plurality of particles 60 to cells in a tissue. The method is initiated in step 1302 by igniting a chemical charge 34 disposed within the portable device to produce a flame (detonation) that travels as a subsonic wave. In certain particular embodiments, at least one pin 38 receives an electrical input in the form of an electrical ignition pulse. The chemical charge 34 generates a flame upon ignition. When the chemical charge 34 is ignited, the pressure released by the chemical charge 34 in the casing 32 destroys the casing 32, and deflagration causes the first material in the chamber 45 along the axis 28 ( 48) to make it possible to propagate at subsonic speed. The deflagration caused by the pyrotechnic charge 34 creates a propagating subsonic flame. In this way, the subsonic flame propagates along the axis 28 towards the material 48 , 52 disposed within the chamber 45 .

Then, in step 1304, materials 48 and 52 are ignited by a flame to produce supersonic waves. In a particular embodiment, the first material 48 is a deflagration-detonation transition (DDT) material. When ignited, the first material 48 transitions from deflagration to detonation (detonation). While the first material 48 is ignited by the subsonic flame, the subsonic flame finally transitions to a detonation (explosion). The flame front accelerates and becomes a supersonic flame propagating the second material 52 .

Then, at step 1306 , the supersonic wave continues to propagate along axis 28 towards wall segment 45 of the portable device. At step 1308 , the method continues by propagating a supersonic wave through the wall segment 45 without rupturing the wall segment 45 . The method continues at step 1310 by causing the supersonic wave to collide with a plurality of particles 60 after passing through the wall segment 45 , thereby accelerating the plurality of particles 60 to a certain velocity. . In this way, the detonation (explosion) wave ejects the plurality of particles 60 from the main body 14 at an initial velocity exceeding the speed of sound.

In certain particular embodiments, the method further comprises penetrating the plurality of particles ( 60 ) through the tissue. In certain specific embodiments, the method further comprises penetrating cells of the tissue through the plurality of particles ( 60 ). In certain specific embodiments, the speed is supersonic. In certain embodiments, the supersonic speed exceeds the speed of sound in hydrogen. In certain particular embodiments, the materials 48 , 52 are one or more of a deflagration-detonation transition (DDT) material and a detonation output material. In certain particular embodiments, the plurality of particles 60 are in contact with the outer surface 56 of the portable device and are generally aligned (arranged in a row) with the axis 28 .

Regarding the above embodiments, the following additional notes are also shown.

(Annex 1)

an accelerator module coupled to the initiator module and configured to generate a supersonic wave from the subsonic wave generated by the initiator module;

The supersonic wave is configured to deliver particles to cells in the tissue,

The accelerator module is

A body having a propagation axis and defining a container having a bottom surface, the container having a first portion and a second portion disposed between the first portion and the bottom surface;

a first material disposed on the first portion;

a second material disposed on the second portion;

a wall segment defined at least in part between the bottom surface of the container and the exterior surface of the body;

a plurality of doped metal particles contacting the outer surface of the body and generally aligned with the lower surface along the propagation axis

to provide

the first material and the second material are configured to be ignited by the subsonic wave generated by the initiator module to produce a supersonic wave, the supersonic wave passing through the wall segment and displacing the plurality of doped metal particles configured to accelerate to a certain speed,

accelerator module.

(Annex 2)

The accelerator module according to Annex 1, wherein the speed is supersonic.

(Annex 3)

The accelerator module according to Annex 1 or 2, wherein said velocity is a velocity sufficient to penetrate said cells in said tissue.

(Annex 4)

The accelerator module of any of Supplementary Notes 1-3, wherein the first material is a deflagration-detonation transition (DDT) material.

(Annex 5)

The accelerator module according to Annex 4, wherein the deflagration-detonation transition material comprises a dry explosive.

(Annex 6)

The accelerator module according to Annex 4 or 5, wherein the deflagration-detonation transition material comprises lead azide.

(Annex 7)

The accelerator module according to any one of Supplementary Notes 4 to 6, wherein the deflagration-detonation transition material comprises copper(I)5-nitrotetrazolate (DBX-1).

(Annex 8)

The accelerator module according to any one of Supplementary Notes 1 to 7, wherein the second material is a detonation output material.

(Annex 9)

The accelerator module according to Supplementary Note 8, wherein the detonation output material is a dry explosive.

(Annex 10)

The accelerator module according to Supplementary Note 8 or 9, wherein the detonation output material contains pentaerythritol tetranitrate (PETN).

(Annex 11)

The accelerator module of any of Supplementary Notes 1-10, wherein the wall segments comprise stainless steel.

(Annex 12)

The accelerator module according to any one of Supplementary Notes 1 to 11, wherein the body has the wall segment.

(Annex 13)

The accelerator module of any of Supplementary Notes 1 to 12, wherein the material of the wall segment is selected such that the wall segment does not rupture when the supersonic wave passes through.

(Annex 14)

The accelerator module according to any one of Supplementary Notes 1 to 13, wherein the thickness of the wall segment is selected such that the wall segment does not rupture when the supersonic wave passes through.

(Annex 15)

The accelerator module according to any one of Supplementary Notes 1 to 14, wherein the body has a base and a cap, and wherein the cap is secured to the base to form at least a portion of the container between the base and the cap.

(Annex 16)

The container is further configured to receive at least a portion of the initiator module when the cap is not secured to the base, the container securing the initiator module relative to the body when the cap is secured to the base The accelerator module according to Annex 15, configured to:

(Annex 17)

Supplementary Notes 1 to 16, wherein the body includes an opening into the container, the opening sized and shaped to allow a portion of the initiator module to pass through the opening when the initiator module is connected to the accelerator module. The accelerator module described in any of.

(Annex 18)

The accelerator module according to Annex 17, wherein a portion of the initiator module is at least one electrical pin.

(Annex 19)

wherein the body has an ejection canister disposed on an opposite side of the wall segment as viewed from the container, the ejection canister aligned with the propagation axis, and wherein the plurality of doped metal particles are disposed within the ejection canister. The accelerator module according to any one of 1 to 18.

(Supplementary 20)

The accelerator module according to Supplementary Note 19, wherein the injection cylinder is a linear cylinder, and a cross section of the injection cylinder has the same size as that of the container.

(Annex 21)

The accelerator module according to any one of Supplementary Notes 1 to 20, wherein the accelerator module is a constituent part of a gene gun.

(Supplementary 22)

The accelerator module of any of Supplementary Notes 1 to 21, wherein the first portion and the second portion are aligned along the propagation axis.

(Annex 23)

The accelerator module according to any one of Supplementary Notes 1 to 22, wherein the bottom surface is perpendicular to the propagation axis.

(Annex 24)

The accelerator module of any of Supplementary Notes 1 to 23, further comprising an adhesive disposed on at least a portion of the outer surface of the body, wherein the plurality of doped metal particles are suspended in the adhesive.

(Supplementary 25)

a screen fixed to the body at a position covering the plurality of doped metal particles;

an adhesive disposed on the screen to inhibit the plurality of doped metal particles from passing through the screen in the absence of supersonic waves

The accelerator module according to any one of Supplementary Notes 1 to 24, further comprising:

(Annex 26)

any of supplementary notes 1 to 25, further comprising a sealant, wherein the container is further configured to receive at least a portion of the initiator module, the sealant disposed within the container to form a seal with the initiator module The accelerator module described in

(Annex 27)

The accelerator module of any of Supplementary Notes 1 to 26, wherein the particles of the plurality of doped metal particles have a diameter of about 1 micrometer.

(Supplementary 28)

The accelerator module of any of Supplementary Notes 1 to 27, wherein the plurality of doped metal particles comprises gold.

(Annex 29)

The accelerator module of any of Supplementary Notes 1-28, wherein the plurality of doped metal particles comprises tungsten.

(Supplementary 30)

The accelerator module of any of Supplementary Notes 1 to 29, wherein the plurality of doped metal particles comprises a chemical substance.

(Annex 31)

The accelerator module according to Annex 30, wherein the chemical substance is DNA.

(Annex 32)

The accelerator module according to any one of Supplementary Notes 1 to 31, wherein the initiator module is an electric detonator (EED).

(Annex 33)

The accelerator module according to Supplementary Note 32, wherein the electric detonator (EED) has an electric input and a chemical output.

(Annex 34)

The accelerator module according to Supplementary Note 33, wherein the chemical output unit is a mixture of zirconium and potassium perchlorate.

(Annex 35)

The accelerator module according to Annex 33 or 34, wherein the electro-explosive device (EED) has a casing and the chemical output is arranged in the casing.

(Annex 36)

The accelerator module according to Supplementary Note 35, wherein the casing is metal.

(Annex 37)

A body having a propagation axis and defining a container having a bottom surface, the body passing through the bottom surface;

a material disposed within the vessel and configured to at least partially produce a supersonic propagating detonation wave;

a wall segment defined at least in part between the bottom surface of the container and the outer surface of the body, the wall segment sized to allow the detonation wave to travel through without breaking the wall segment;

a plurality of doped metal particles disposed on opposite sides of the wall segment as viewed from the vessel and approximately aligned with the axis of propagation

comprising, an accelerator module.

(Supplementary 38)

The accelerator module according to supplementary note 37, wherein the plurality of doped metal particles are in contact with the outer surface of the body.

(Supplementary 39)

The accelerator module according to Annex 37 or 38, wherein the propagation axis is perpendicular to the bottom surface.

(Supplementary 40)

The accelerator module of any of Supplementary Notes 37 to 39, wherein the material comprises a deflagration-detonation transition material (DDT).

(Annex 41)

The accelerator module of any of Supplementary Notes 37-40, wherein the material comprises a detonation output material.

(Annex 42)

The container comprises a first portion and a second portion, the second portion disposed between the first portion and the bottom surface, the material comprising a first material and a second material, the first material comprising: The accelerator module of any of Supplementary Notes 37 to 41, wherein the accelerator module is disposed in the first portion and the second material is disposed in the second portion.

(Annex 43)

The accelerator module of any of Supplementary Notes 37 to 42, wherein the accelerator module is configured to be coupled to an initiator module, the initiator module being configured to ignite the material at subsonic waves.

(Annex 44)

The accelerator module of any of Supplementary Notes 37 to 43, wherein the detonation wave accelerates the plurality of doped metal particles after passing through the wall segment.

(Supplementary 45)

An aspect of excluding a plurality of doped metal particles into a cell (preferably a cell in a tissue) using a portable device and a cell (preferably a cell in a tissue) in a state existing in a human subject (living body) In addition, it is a method for delivering to a cell (preferably, an aspect excluding cells in a tissue) in a state existing in an individual (living body) of an animal is also preferred),

igniting a chemical charge disposed within the portable device to generate a subsonic wave to propagate the subsonic wave along an axis toward a material disposed within the portable device;

igniting the material by the subsonic wave to generate a supersonic wave, which continues to propagate the supersonic wave along the axis towards a wall segment of the portable device;

propagating the supersonic wave through the wall segment without rupturing the wall segment, causing the supersonic wave to impinge upon the plurality of doped metal particles after passing through the wall segment, thereby destroying the plurality of doped metal particles. to accelerate to speed

How to include.

(Annex 46)

The method according to Annex 45, further comprising penetrating the tissue with the plurality of doped metal particles.

(Annex 47)

The method of Annex 46, further comprising penetrating said plurality of doped metal particles into cells of said tissue.

(Supplementary 48)

The method according to any one of Annexes 45 to 47, wherein the velocity is supersonic.

(Annex 49)

The method according to Annex 48, wherein the supersonic speed is a speed exceeding the speed of sound in hydrogen.

(Supplementary 50)

The method according to any one of Annexes 45 to 49, wherein the material is a deflagration-detonation transition material (DDT).

(Supplementary 51)

The method according to any one of Supplementary Notes 45 to 50, wherein the material is a detonation output material.

(Supplementary 52)

The method of any of Supplementary Notes 45-51, wherein the plurality of doped metal particles are in contact with the outer surface of the portable device and are generally aligned with the axis.

(Annex 53)

a gene gun having a propagation axis extending between at least the chemical charge and the plurality of doped metal particles,

a deflagration-detonation transition material (DDT) disposed approximately along the propagation axis;

a detonation output material disposed on the opposite side of the deflagration-detonation transition material (DDT) as viewed from the chemical charge and disposed approximately along the propagation axis;

a wall segment separating the detonation output material from the plurality of doped metal particles

comprising, a gene gun.

(Annex 54)

The gene gun according to Supplementary Note 53, wherein said wall segment has a size that does not rupture in response to detonation of said detonation output material.

(Supplementary 55)

An accelerator module connected to the initiator module and configured to deliver the particles to cells in the tissue and a plurality of doped metal particles,

a body having a propagation axis and defining a container having a bottom;

a material disposed in the container to generate a supersonic wave by being ignited by the subsonic wave generated by the initiator module;

A wall segment spaced through the propagation axis to the interior and exterior of the vessel.

to provide

on the outer surface of the wall segment, disposable to align a plurality of doped metal particles along the propagation axis;

the supersonic wave generated by the material generating the supersonic wave accelerates the plurality of doped metal particles by impinging on the plurality of doped metal particles after propagating and passing through the wall segment;

accelerator module.

(Annex 56)

The accelerator module according to Supplementary Note 55, wherein the material generating the supersonic wave generates a detonation wave traveling at supersonic speed by being ignited by the subsonic wave.

(Annex 57)

The accelerator module according to Annex 55 or 56, wherein the material for generating the supersonic wave is a dry explosive.

(Supplementary 58)

The accelerator module according to any one of Supplementary Notes 55 to 57, wherein the bottom surface is perpendicular to the propagation axis.

(Supplementary 59)

The accelerator module of any of Supplementary Notes 55-58, wherein the wall segment is configured not to rupture when the supersonic wave passes through.

(Supplementary 60)

Supplementary Note 55, wherein the body has an ejection canister disposed on an opposite side of the wall segment as viewed from the container, the ejection canister aligned with the propagation axis, and wherein the plurality of doped metal particles are disposed within the ejection canister. The accelerator module of any of claims-59.

(Annex 61)

The container includes a first portion and a second portion disposed between the first portion and the bottom surface,

wherein the material comprises a first material disposed in the first portion and a second material disposed in the second portion;

The accelerator module of any of Annexes 55 to 60.

(Annex 62)

The accelerator module of supplementary note 61, wherein the first portion and the second portion are aligned along the propagation axis.

(Annex 63)

The accelerator module according to Annex 61 or 62, wherein the first material is a deflagration-detonation transition (DDT) material.

(Annex 64)

The accelerator module according to Annex 63, wherein the deflagration-detonation transition (DDT) material comprises at least one of lead azide and copper(I)5-nitrotetrazolate (DBX-1).

(Annex 65)

The accelerator module according to any one of Supplementary Notes 61 to 64, wherein the second material is a detonation output material.

(Supplementary 66)

The accelerator module according to Supplementary Note 65, wherein the detonation output material contains pentaerythritol tetranitrate (PETN).

(Annex 67)

The accelerator module according to any one of notes 55 to 66, wherein the initiator module has a pyrotechnic charge and ignites the pyrotechnic charge to generate the subsonic wave.

(Annex 68)

A gene gun comprising the accelerator module according to any one of Supplementary Notes 55 to 67.

(Annex 69)

An aspect of excluding a plurality of doped metal particles into a cell (preferably a cell in a tissue) using a portable device and a cell (preferably a cell in a tissue) in a state existing in a human subject (living body) In addition, it is a method for delivering to a cell in a state existing in an animal (living body) (preferably, an aspect excluding cells in a tissue) is also preferred),

igniting a chemical charge disposed within the portable device to generate a subsonic wave to propagate the subsonic wave along an axis toward a material disposed within the portable device;

igniting the material by the subsonic wave to generate a supersonic wave, which continues to propagate the supersonic wave along the axis towards a wall segment of the portable device;

propagating the supersonic wave through the wall segment, causing the supersonic wave to impinge upon the plurality of doped metal particles after passing through the wall segment, thereby accelerating the plurality of doped metal particles.

How to include.

<Term>

Although specific embodiments and examples are disclosed herein, the subject matter of the present invention goes beyond the examples in the specifically disclosed embodiments to other alternative embodiments and/or uses, and modifications and equivalents thereof. . Accordingly, the scope of the claims appended hereto is not limited by any of the specific embodiments described above. For example, in any method or process disclosed herein, the operation or process (operation) of the method or process may be performed in any suitable order, and is not necessarily limited to a particular disclosed order. Various processes (operations) may be sequentially described as a plurality of separate processes (operations) in a way that may be helpful in understanding a particular embodiment, but the order of the description is that these processes (operations) are in order should not be construed to imply reliance on In addition, structures, systems, and/or apparatuses described herein may be implemented as integrated components or as separate components. For the purpose of comparing the various embodiments, specific aspects and advantages of these embodiments are described. Thus, for example, various embodiments may achieve one aspect, advantage, or set of advantages as taught herein, but not necessarily other aspects or advantages as may be taught or suggested herein. This can be done in an optimizing way.

A feature, material, characteristic, or combination thereof described in connection with a particular aspect, embodiment, or embodiment is compatible with any other aspect, embodiment, or embodiment described in the main body of this specification or elsewhere, as long as they It should be understood that it is applicable to All features disclosed herein (including the appended claims, abstracts and drawings), and/or all steps of any method or process so disclosed, are provided that at least some of those features and/or steps are mutually exclusive. Except, it can be combined in any combination. Not necessarily all such aspects or advantages may be achieved by a particular embodiment. For example, one or more features may include: 1) a combination of DDT and PETN, 2) a chemical charge (explosive), a DDT disposed downstream of the chemical charge, and a PETN disposed downstream of the DDT, 3) an initiator an accelerator module configured to receive the module; 4) a wall segment that separates the detonation output material from the doped metal particles; 5) a detonation (blast) wave passing through the wall segment without destroying the wall segment; 6) exceeding the speed of sound igniting the detonation (detonation) wave using doped metal particles achieving a velocity of Therefore, protection is not limited to the detail of the above-mentioned embodiment. Protection means any novel one, or any novel combination of features, disclosed herein (including the appended claims, abstract and drawings) or any novelty of any step of any method or process so disclosed. one or any novel combination.

Also, certain features that are described in the present disclosure in the context of separate implementations may be implemented in combination in a single implementation. Conversely, various features that are described in the context of a single implementation may also be implemented in multiple implementations individually or in any suitable sub-combination. Also, while features may be described above as acting in a particular combination, one or more features from the claimed combination may, in some cases, be cut out from the combination, the combination being a sub-combination or variant of a sub-combination. may be claimed as

Further, although processes may be shown in the drawings or described herein in a particular order, such processes need not all be performed in the particular order or sequential order in which they appear to achieve a desired result. Other processes not shown or described may be incorporated into the exemplary methods and processes. For example, one or a plurality of additional processes may be performed before, after, concurrently with, or between the processes described. In addition, the process may be rearranged or reordered in another implementation. Those skilled in the art will understand that in some embodiments, the actual steps taken in the illustrated and/or disclosed processes may differ from those illustrated in the drawings. Depending on the embodiment, some of the above steps may be omitted, and other steps may be added. In addition, the features and characteristics of the specific embodiments disclosed above may be combined in different ways to form further embodiments, all of which are within the scope of the present disclosure. In addition, the separation of various system components in the above embodiments should not be construed as requiring such separation in all embodiments, and the components and systems described are generally integrated into a single product, or a plurality of It should be understood that it can be packaged as a product of

For purposes of the present disclosure, certain aspects, advantages, and novel features are described herein. It cannot necessarily be said that all such advantages can be achieved in accordance with a particular embodiment. Thus, for example, one skilled in the art will realize that the present disclosure may be embodied or practiced in a manner that achieves one advantage or set of advantages taught herein, but not necessarily other advantages that may be taught or suggested herein. will recognize that

For descriptive purposes, the term "horizontal" as used herein, regardless of its orientation, means It is defined as a plane. The term "floor" can be substituted with the term "floor". The term "vertical", as defined, refers to a direction perpendicular to the horizontal. “above”, “below”, “bottom”, “top”, “side”, “higher”, “lower”, “ Terms such as "upper", "over" and "under" are defined with respect to the horizontal plane.

In particular, the conditional terms used herein, such as "can", "could", "might, may", "for example (e.g.)", etc. In general, it is conveyed that certain embodiments include certain features, elements, and/or steps, but other embodiments do not, unless specifically indicated otherwise, or otherwise understood in the context in which it is used. are intending Thus, such conditional terms generally refer to that a feature, element, and/or step is required in some form for one or more embodiments, or with or without other inputs or instructions for one or more embodiments. Without it, it is not implied that these features, elements, and/or steps necessarily include logic for determining whether or not these features, elements, and/or steps are included in, or are to be executed in, any particular embodiment. . Terms such as “comprising”, “comprising” and “having” are synonyms, and are used in an open-end manner inclusively, and do not exclude additional elements, features, operations, operations, and the like. In addition, since the term "or" is used in its inclusive meaning (not an exclusive meaning), for example, when used to connect a list of elements, the term "or" is One, several, or all of the elements.

Conjunctions such as the phrase "at least one of X, Y and Z", unless otherwise specified, apart from the context generally used to convey that an article, term, etc. may be any of X, Y or Z, apart from the context It is understood. Thus, these conjunctions generally do not imply that a particular embodiment requires the presence of at least one of X, at least one of Y, and at least one of Z.

As used herein, the term "approximately", "about", "generally" and "substantially", etc., as used herein, "language of degree" means a value, amount close to a stated value, amount, or characteristic. or exhibits a characteristic and still performs a desired function or achieves a desired result. For example, the terms “approximately”, “about”, “generally” and “substantially” refer to less than 10%, less than 5%, less than 1%, less than 0.1%, and less than 0.01% of the stated amount. In some cases, it refers to the amount within. As another example, in certain embodiments, the terms "generally parallel" and "substantially parallel" are not strictly parallel to 15 degrees, 10 degrees, 5 degrees, 3 degrees, 1 degree, 0.1 degrees, or otherwise. It refers to a value, amount, or characteristic that deviates by the following.

Although the gene gun has been disclosed in the context of specific embodiments and examples, the gene gun extends beyond the specifically disclosed embodiments to other alternative embodiments and/or uses of the embodiments, and modifications and equivalents thereof. , will be understood by those skilled in the art. Accordingly, the scope of the gene gun disclosed herein should not be limited by the specific disclosed embodiments described above, but should be determined only by impartial reading of the following claims.

Each aspect disclosed herein may be combined with any feature other than those disclosed herein.

10: gene gun
11: handle
12: accelerator module
14: body
16: Donate
20: courage
30: Initiator
32: casing
34: Chemical Charge
44: wall segment
45: chamber
46: first part
48: first material
50: second part
52: second material
54: bottom
58: injection barrel
60: particle

Claims (14)

An accelerator module connected to the initiator module and configured to deliver the particles to cells in the tissue and a plurality of doped metal particles,
a body having a propagation axis and defining a container having a bottom;
a material disposed in the container to generate a supersonic wave by being ignited by the subsonic wave generated by the initiator module;
A wall segment spaced through the propagation axis to the interior and exterior of the vessel.
to provide
on the outer surface of the wall segment, disposable to align a plurality of doped metal particles along the propagation axis;
the supersonic wave generated by the material generating the supersonic wave accelerates the plurality of doped metal particles by impinging on the plurality of doped metal particles after propagating and passing through the wall segment;
accelerator module. The accelerator module of claim 1 , wherein the supersonic wave generating material generates a supersonic propagating detonation wave by being ignited by the subsonic wave. 3. The accelerator module according to claim 1 or 2, wherein the material for generating the supersonic wave is a dry explosive. 4. The accelerator module according to any one of claims 1 to 3, wherein the bottom surface is perpendicular to the propagation axis. 5. The accelerator module of any preceding claim, wherein the wall segment is configured to not rupture when the supersonic wave passes through. 6. The body of any one of the preceding claims, wherein the body includes an injection barrel disposed on an opposite side of the wall segment as viewed from the container, the injection barrel aligned with the propagation axis, and wherein the plurality of injection barrels are aligned with the propagation axis. doped metal particles are disposed within the ejection barrel. 7. The container according to any one of claims 1 to 6, wherein the container has a first portion and a second portion disposed between the first portion and the bottom surface;
wherein the material comprises a first material disposed in the first portion and a second material disposed in the second portion;
accelerator module. 8. The accelerator module of claim 7, wherein the first portion and the second portion are aligned along the propagation axis. 9. The accelerator module of claim 7 or 8, wherein the first material is a deflagration-detonation transition (DDT) material. The accelerator module of claim 9 , wherein the deflagration-detonation transition (DDT) material comprises at least one of lead azide and copper(I)5-nitrotetrazolate (DBX-1). 11. The accelerator module according to any one of claims 7 to 10, wherein the second material is a detonation output material. 12. The accelerator module of claim 11, wherein the detonation output material comprises pentaerythritol tetranitrate (PETN). 13 . The accelerator module according to claim 1 , wherein the initiator module has a chemical charge and ignites the chemical charge to generate the subsonic wave. A gene gun comprising the accelerator module according to any one of claims 1 to 13.

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